JOURNAL OF OPTOELECTRONICS AND ADVANCED MATERIALS Vol. 9, No. 9, September 2007, p.

2910 - 2916

Introducing logistic enzyme kinetics

M. V. PUTZ*, A. M. LACRMa, V. OSTAFEa
Laboratory of Computational and Structural Physical Chemistry, Chemistry Department, West University of Timioara,
Pestalozzi Street No.16, Timioara, RO-300115, Romania
a
Laboratory of Biochemistry, Chemistry Department, West University of Timioara, Pestalozzi Street No.16, Timioara,
RO-300115, Romania
For treatment of in vitro enzyme kinetics the Michaelis-Menten equation is generalized to a logistic form. From the new
probabilistic viewpoint the classical Michaelis-Menten kinetic resembles the first order expansion of the logistic one with
respect to the bound substrate concentration. The probabilistic approach has three advantages. First, it better describes the
quasi steady state approximation of catalysis. Second, it substitutes a logistic analytical solution for the closed-form WLambert solution for the progress curves of the substrate decay or product formation, this way recovering the previously
introduced ansatz by M. V. Putz, A.-M. Lacrm and V. Ostafe Int. J. Mol. Sci. 7, 439 (2006). Finally, it provides an
alternative time-dependent fitting curve for estimating kinetic parameters that replaces the earlier linear plot representation
with a first order of time expansion.
(Received January 15, 2007; accepted August 24, 2007)
Keywords: Michaelis-Menten equation, Logistic equation, Quasi steady-state approximation, Progress curves, Fitting equations

1. Introduction
It has long been recognized that the chemical
reactions that support life are mediated by enzymes and
their kinetics. Brown [1, 2] and Henri [3, 4] first proposed
that enzyme catalysis is based on the reversible reaction
between and enzyme E and a substrate S with rate constant
k1 to form an intermediate enzyme-substrate complex ES.
The complex then reacts irreversibly with rate constant k2,
regenerating the enzyme E and producing product P:
k1

k2

E + S ES E + P .
k1

(1)

The mathematical formulation of this process was

developed by Michaelis-Menten [5] and is represented by
the
classical
Michaelis-Menten
equation
(2)
where Vmax = k 2 [ E 0 ] , and K M = (k 1 + k 2 ) / k1 .

V [S ]
d

[ S ](t ) = v0 = max 0
[S 0 ] + K M
dt
t =0

(2)

Solution of the Michaelis-Menten equation to estimate

the kinetic constants has traditionally involved linear
transformation [6, 7] or the use of graphical methods [810] both of which are subject to error. For example, when
the double reciprocal linear plot of equation (2) is used,
small errors in [ S 0 ] or v0 lead to large errors in 1 /[ S 0 ]
or 1 / v 0 and thus to large errors in K M and Vmax [11,
12]. On the other hand, direct application of equation (2)
requires an estimate of the initial velocity for every point
to be fitted to the progress curve [13, 14].
Integration of equation (2) provides an instantaneous
version of the Michaelis-Menten equation [15, 16] as
equation (3), which also has equivalent linear forms for a
number of different cases [17].

[ S ](t )

Vmax t = ([ S 0 ] [ S ](t ) ) K M ln
[S 0 ]

(3)

Working formulas developed for particular cases such

as enzyme inhibition, by Duggleby and Morrison [18],
multiple substrates, by Duggleby and Wood [19], the
presence of an inhibitor at concentrations comparable to
the enzyme concentration, by Szedlacsek et al. [20], and
gradual inactivation of an enzyme, by Duggleby [21],
ignore the fact that the largest experimental error is in the
concentration and not in the velocity. Because of this, the
linear transformations and approximations distort the
experimental errors, leading to possible bias in the
estimates of K M and Vmax [14]. Schnell and Mendoza
[13] derived the closed form solution (4) of the
instantaneous Michaelis-Menten equation in terms of the
W-Lambert function [22].

[ S ] [ S0 ]Vmaxt
[ S ]W (t ) = K M W 0 e K M
K
M

(4)

Relationship (4) is valid at all times and makes it

possible to treat many complex enzymatic interactions
mathematically, extensively studied by Schnell and
Mendoza [14, 22, 23]. This model is, however, limited
because the W- function is not widely available in curvefitting software.
More generally, it has been shown that the
computational methods used to numerically integrate the
instantaneous Michaelis-Menten equation are timeconsuming and relatively slow [24-26].
In the present work we propose a generalized version
of the classical Michaelis-Menten equation that avoids
most of the difficulties encountered in modeling enzymatic
kinetics in vitro.

2911

Introducing logistic enzyme kinetics

2. Theoretical model
In the post genomic era the development of kinetic
models that allow simulation of complicated metabolic
pathways and protein interactions is becoming
increasingly important [27,28]. Unfortunately, the
difference between an in vivo biological system and
homogeneous in vitro conditions is large, as shown by
Schnell and Turner [29]. Mathematical treatments of
biochemical kinetics have been developed from the law of
mass action in vitro but the modifications required to bring
them in line with the stochastic in vivo situation are still
under development [30-32].
We use a probabilistic approach, based on the law of
mass action, to characterize in vitro enzymatic reactions of
type (1):
1 = PREACT ([ S ]bind ) + PUNREACT ([ S ]bind ) . (5)
In equation (5), PREACT ([ S ]bind ) is the probability
that the reactions (1) proceed at a certain concentration of
substrate binding to the enzyme [ S]bind . The limits are:

0 , [ S ]bind 0
PREACT ([ S ]bind ) =
1 , [ S ]bind >> 0

PREACT ([ S ]bind ) = 0

(6)

when the enzymatic reaction

after the initial transient of the enzyme-substrate reaction

in (1).
We know only that expression (9) behaves like a
probability function, with values in the realm [0, 1]. Given
expressions (2), (5) and (9) we derive an expression for the
unreacted probability term, PUNREACT ([ S ](t )) .
The expression:

PUNREACT ([ S ](t )) MM =

KM
[ S ](t ) + K M

(10)

satisfies all of the probability requirements, including the

limits in (7), and, when combined with equations (9) and
(5), gives the instantaneous version of the classical
Michaelis-Menten equation (2). Remarkably, expression
(10) can be seeing as generalization of the efficiency of the
Michaelis-Menten reaction under steady-state conditions
[34]. Originally, the efficiency depends on two
parameters: K M that embodies the thermodynamic
conditions of the enzymic reaction and the initial substrate
concentration [ S 0 ] ; it determines the ratio of the free to
total enzyme concentration in the reactions (1); that is,
when the efficiency is equal to one, we cannot expect to
find substrate free in the reaction, i.e. the reactions in (1)
are all consumed so that first branch of the limits (7) is
fulfilled as no further binding will occur.

does not proceed or when it stops because the substrate

fails to bind or is entirely consumed. Conversely,
PREACT ([ S ]bind ) = 1 when the enzymatic reaction
proceeds, and it is related to the standard quasi-steadystates approximation (QSSA). The probability of the
occurrence of products in reactions (1) lies between these
limits. Similarly, in the case where enzymatic catalysis
does not take place, PUNREACT ([ S ]bind ) , the limits are:

1 , [ S ]bind 0
0 , [ S ]bind >> 0

PUNREACT ([ S ]bind ) =

(7)

This probabilistic treatment of enzymatic kinetics is

based on the chemical bonding behavior of enzymes that
act upon substrate molecules through diverse mechanisms
and it may offer the key to the quantitative treatment of
different types of enzyme catalysis [33].
To expand the terms of equation (5) to analyze
reactions in the (1) we first recognize that the binding
substrate concentration can be treated as the instantaneous
substrate concentration: [ S ]bind = [ S ](t ) .
Maintaining the quasi-steady-state conditions for in
vitro systems, we may assume constant associationdissociation rates so that probability of reaction is written
as the rate of consumption of the substrate,

v(t ) =

d
[ S ](t )
dt

(8)

to saturation:

PREACT ([ S ](t )) =

v(t )
1 d
=
[ S ](t )
Vmax
Vmax dt

Fig. 1. Initial Michaelis-Menten and logistic velocities

plotted against initial substrate concentration for the
reaction (1). The dashed curve corresponds to the
Michaelis-Menten equation (2) while the continuous
thick curve represents its logistic generalization:

v0* = Vmax [1 exp( [ S 0 ] / K M )]

It is clear that the Michaelis-Menten term (10) is just a

particular choice for a probabilistic enzymatic kinetic
model of the conservation law (5). A more generalized
version of equation (10) that preserves all of the above
probabilistic features is

PUNREACT ([ S ](t )) = e
*

(9)

[ S ](t )
KM

(11)

2912

M. V. Putz, A. M. Lacrm, V. Ostafe

from which the Michaelis-Menten term (10) is returned by

performing the [ S ](t ) first order expansion for the case
where the bound substrate approaches zero:
[ S ](t )0

PUNREACT ([ S ](t ))* =

e

[ S ]( t )
KM

1
= PUNREACT ([ S ](t )) MM
[ S ](t )
1+
KM

.
(12)
Worth noting that there is no monotonically form
between 0 and 1 other that that of equation (11) to
reproduce basic Michaelis-Menten term (10) when
approximated for small x = [S](t)/KM . For instance, if one
decides to use exp(-x2) then the unreactive probability will
give 1/(1+x2) as the approximation for small x, definitely
different of what expected in basic Michaelis-Menten
treatment (10). This way, the physico-chemical meaning
of equation (12) is that the Michaelis-Menten term (10)
and its associated kinetics apply to fast enzymatic
reactions, i.e. for fast consumption of [S](t), which also
explains the earlier relative success in applying
linearization and graphical analysis to the initial velocity
equation (2).
Use of equation (11) instead of (10) expands the range
of reaction rates and provides a new kinetic equation, in
the form of a logistic expression

1
Vmax

d
[ S ](t ) = 1 e
dt

[ S ]( t )

KM

(13)

based on probability and derived from equations and (5),

(9), and (11).
At initial conditions, logistic equation (13) gives an
*

initial velocity of reaction ( v0 ) that is uniformly higher

than that calculated by Michaelis-Menten (2) at all initial
concentrations of the substrate, except for the case where
[ S 0 ] 0 , when both are zero, see Fig. 1.
Reliability tests of the logistic form of MichaelisMenten kinetics (13) are reported below.

3. Reliability of the logistic enzyme kinetic

Quasi Steady-State Approximation Analysis
One of the fundamental assumptions made in deriving
basic Michaelis-Menten kinetics, except in the initial socalled transient phase of the reaction, is the quasi steady
state approximation of the [ES] concentration, i.e. the rate
of synthesis of the ES complex must equal its rate of
consumption until the substrate is nearly exhausted. It has
been demonstrated that the QSSA is equivalent with the
physiologically common condition that the substrate is in
great excess over the enzyme, as firstly shown by Laidler
[35]:
[ S 0 ] >> [ E 0 ] .
(14)
Let us investigate whether condition (14) may arise
within the proposed probabilistic enzymatic kinetics and

what consequences that has for applicability of the logistic

treatment.
For reaction (1) to proceed with a high probability it is
necessary that

PREACT ([ S ]bind ) 1 PUNREACT ([ S ]bind ) 0

(15)
or, the probability of the enzymatic reaction proceeding
increases to one as the probability that the substrate will
not bind with the enzyme approaches zero. Analytically,
we use the limiting case (16) where reaction (1) proceeds.

PREACT ([ S ](t )) = 1

(16)

Then, by combining equation (16) with the general in

vitro form (9), we derive the time dependent equation (17).

Substituting

1
Vmax

d
[ S ](t ) = 1
dt

Vmax = k 2 [ E 0 ]

and

(17)

integrating

produces the linear portion of the substrate depletion

curve:
(18)
[ S ](t ) = [ S 0 ] k 2 [ E 0 ]t .
The substrate condition [ S ](t ) >> 0 corresponds to
the binding case for which equation (16) is valid under the
conditions given in expression (6). Applying this substrate
condition to equation (18) during the rate limiting step
when

1
k2

(19)

ensures that almost all of the substrate is being

transformed into product via reactions (1), resulting in the
QSSA condition (14).
We have proved that the left side of the probabilistic
equivalence (15) is valid for QSSA and we must do the
same for the right side.
The more closely
PUNREACT ([ S ](t )) approaches zero as PREACT ([ S ](t ))
approaches one, the better QSSA is obtained.
Recalling the two forms presented for the non-binding
reactivity, the Michaelis-Menten in equation (10) and the
logistic in equation (11), we can clearly see that the
following hierarchy exists
PUNREACT ([ S ](t )) MM =

1
1
> [ S ](t ) = PUNREACT ([ S ](t )) *
[ S ](t )
1+
e KM
KM

(20)
regardless of the time at which they are compared.
Therefore, because the logistic probability PUNREACT is
lower than the Michaelis-Menten at all times, QSSA is
better satisfied using the logistic approach.

2913

Introducing logistic enzyme kinetics

Full Time Course Analysis

Many biochemists use the velocity equations for
kinetic parameter estimates despite the fact that the rates
are difficult to determine experimentally. In practice either
the substrate depletion or the product formation is
measured as a function of time and the rates are calculated
by differentiating the data, leading to an inexact analysis
[13, 23]. Alternatively, the differential equations
governing the biochemical reactions may be solved or
approximated to obtain reactant concentration as function
of time. This approach decreases the number of
experimental assays by at least a factor of five, as proved
by Schnell and Mendoza [14], because multiple
experimental points may be collected for each single
reaction.
Unfortunately, until now, the most general analytical
time-dependent solution for reaction (1) used the closed
form (4) that has many mathematical disadvantages. For
example it can return multiple values for the same
argument [36] or result in an infinitely iterated exponential
function [24].
To test whether the logistic kinetic equation (13),
which is a natural generalization of the Michaelis-Menten
equation, may provide a workable analytical solution in an
elementary form we first integrate the equation
[ S ](t )

[ S0 ]

d [ S ](t )
= Vmax dt
exp( [ S ](t ) / K M ) 1 0

(21)

[ S ] L (t ) = K M

V
t
[ S0 ]

max

KM KM
1 . (27)
ln1 + e
e

This time-dependent solution (27) substitutes an

elementary logarithmic dependency for the W-Lambert
function. It is remarkable that the solution of a generalized
logistic kinetic version of the Michaelis-Menten
instantaneous equation provides an analytically exact
solution.
The cutting test is in the comparison of the progress
curves generated by the W-Lambert (4) and logistic
solutions (27) respectively. To do this, the following
working formulas for the instantaneous complex [ES](t),
product [P](t) and enzyme [E](t) concentrations are
employed in both the W-Lambert (4) and logistic (27)
versions of the binding substrate concentration, [S]W,L ,
according with Schnell and Mendoza [13]:
[ ES ]W , L (t ) =

[ E 0 ][ S ]W , L (t )
[ S ]W , L (t ) + K M

{1 exp[ k1t ([ S 0 ] + K M )]} ,

[ P ]W , L (t ) = [ S 0 ] [ S ]W , L (t ) [ ES ]W , L (t ) ,
[ E ]W , L (t ) = [ E 0 ] [ ES ]W , L (t ) ,
sW , L (t ) =

[ S ]W , L (t )
[S 0 ]

, eW , L (t ) =

[ E ]W , L (t )
[ E0 ]

, esW , L (t ) =

[ ES ]W , L (t )
[ E0 ]

(28a)
(28b)
(28c)

, pW , L (t ) =

[ P]W , L (t )

(29)

The transformation:

generating the new equation to be solved:

[ S0 ]

[ S ](t )

[ S 0 ] [ S ](t ) + K M ln e K M 1 K M ln e K M 1 = Vmax t

.
(22)

= 1

1
ln(t + e )

(30)

allows us to use scaled time for the abscissa so that an

infinite time range can be mapped onto the interval [0,1].

Although apparently more complex than the previous

version (3), equation (22) can be solved exactly. This can
be demonstrated by substituting

([ S ](t ) ) =

[ S ](t )
KM

into (22) to get the simple equation:

(23)

([ S ](t ) ) ln e ([ S ](t ) ) 1 = (t )

(24)

where we have also introduced the functional notation:

[ S0 ]

1
(Vmax t [S 0 ]) ln e K M 1 . (25)
(t ) =
KM

Now the exact solution of equation (24) is a logistic

expression:

([ S ](t ) ) = ln 1 e (t )

).

(26)

Finally, substituting function (25) into expression (26)

gives the logistic progress curve for substrate consumption
in an analytically elementary form:

Fig. 2. Time dependent behavior of the reactant scaled

concentrations (29) for the paradigmatic enzymesubstrate reaction (1) when the basic (dashed lines) and
generalized logistic (solid lines) versions of the
Michaelis-Menten kinetic are employed, with the
parametric values
k1=k2=102s1, k1=106M1s1,
[S0]=104M, and [E0]=106M, against the scaled time
(30).

Fig. 2 shows the plots of the W-Lambert and logistic

progress curves (29) for an enzyme-catalyzed reaction in

[S 0 ]

2914

M. V. Putz, A. M. Lacrm, V. Ostafe

vitro where k1=k2=102s1, k1=106M1s1, [S0]=104M, and

[E0]=106M.
The quantitative behavior of the reactant
concentrations in both the W-Lambert and logistic cases
are strikingly similar. In addition, time-dependent product
curves may be used instead of the initial velocity curves in
Fig. 1. However, the logistic product curves are smoother
and at higher concentrations than those obtained from the
W-Lambert approach due to the higher probability of
reaction (see the discussion from the previous section).
Having proved the reliability of the logistic timedependent form of the substrate depletion expression (27)
compared to the W-Lambert-based expression (4) we
propose the general transformation [37]:

( (

f1W f 2 e f 2 e f3t f1 ln 1 + e f 2 1 e f3t , (31)

where f1 , f 2 , f 3 are factors that depend on K M and
Vmax , which is used to transform the closed form
solutions of enzymatic kinetics into elementary analytical
expressions. The particular relevance of the replacement
(31) may be visualized from the Fig. 3.
As shown in Fig. 3, the difference in the shape of the
curves generated by the general W-Lambert and natural
logarithm functions (curve a) is almost completely
removed when the W-Lambert time-dependent solution is
replaced with the logistic one transformed as in (31)
(curve b). This result suggests that using this logistic
transformation (31) we get a good time-dependent
representation over a broad range for enzymatic kinetics in
vitro.

alternative substrates [37] or for reversible enzyme

kinetics [38], making them more useful for fitting
laboratory data [39-41].
Analysis of Fitting Curves
Although they are able to use the progress curves for
analysis of the data obtained from experimental assays,
many biochemists prefer to use linear representations of
enzyme kinetics. Instead of using the time-dependent
solution (4), they rearrange the time-dependent equation
(3) to a sort of time-dependent regression expression, for
example, the reciprocal double plot equation:

K
1
t
=
+ M
[ S 0 ] [ S ](t ) Vmax Vmax

[S ]
1

ln 0 .
[
]
[
](
)

[
S
S
t
S ](t )
0

(32)
A plot of equation (32) will yield a straight line with
an intercept of 1 / Vmax and a slope of K M /Vmax from
which the kinetic parameters K M and Vmax can be
obtained.
However, this approach has been criticized [40, 41]
and it is worthwhile to investigate whether the exact
logistic solution (27) may be better for fitting a linear
curve.
First, we take advantage of the fact that the logistic
solution (27) has an elementary form to take its derivative
with respect to time. This provides an expression for the
instantaneous velocity (8) which can be transformed to the
finite difference ([ S 0 ] [ S ](t ) ) / t .
Inversion of the result yields the expression:

t
1
=
+
[ S 0 ] [ S ](t ) Vmax

Fig. 3. a) Comparison of the W-Lambert function

(dashed line) with the logarithmic function (solid line)
against positive ranged simple arguments; b)
Comparison of the W-Lambert function (dashed line)
with logistic function (solid line) when the arguments
include the temporal dependencies as in (31),
respectively, being all involved factors fixed to unity. The
time abscise scale in (b) is taken in arbitrary units.

This procedure can be directly applied to the existing

W-Lambert type solutions for many enzymatic reactions in
vitro, e.g. for enzyme inhibitors, for fully competitive
enzyme reactions, for the enzyme kinetics of multiple

1
[ S0 ]

Vmax e K M 1

Vmax
t
KM

(33)

Fig. 4. Time dependent representation of the fitting

curves (32)-(34) for the parametric values k1=k2=102s1,
k1=106M1s1, [S0]=104M, and [E0]=106M. The dashed
line corresponds to equation (32) and involves the WLambert closed form solution (4). The thin continuous
line is the representation of linear equation (34) while
the thick continuous line is the plot of non-linear
equation (33) being both based on the logistic solution
(27). Abscise and ordinate scales are given in arbitrary
units.

Introducing logistic enzyme kinetics

Equation (33) is not a linear function, although it may

be used for fitting the experimental time series data to
determine the kinetic parameters K M and Vmax . To
obtain a linear equation from expression (33), recall that,
from the probabilistic perspective of enzymatic kinetics,
the Michaelis-Menten equation is valid for fast reactions.
Performing a first order expansion with respect to time on
(33) gives the linear equation:

t
=
[ S 0 ] [ S ](t )

[ S0 ]
KM

e
1
t
+
[
]
[
S
0

S0 ]

Vmax e K M 1 K M e K M 1

(34)
Fig. 4 shows the comparison between linear fitting
equation (32) and the new logistic based expression (34)
along with the nonlinear form (33), for the same
parameters used in Figure 2 above. Generation of the
curve for expression (32) required that the W-Lambert
time-dependence of the substrate depletion be substituted
for the time dependent substrate concentration.
It is clear that the linear logistic curve (34) is nearly
coincident with the Michaelis-Menten curve (32), both
providing linear approximations of the general non-linear
logistic curve (33). This is the first instance of treating
substrate-enzyme binding probabilistically and it has the
advantage of avoiding use of the W-Lambert function,
which is impossible to evaluate exactly. The resulting
linear fitting curves are essentially the same with either
approach.

2915

From a mathematical perspective it is interesting to

note that the more general probabilistic enzymatic kinetic
problem is simpler than the classical Michaelis-Menten
problem because the elementary solutions of the reactant
progress curves and of the fitting equations is in better
agreement with the quasi-steady-state condition. Although
this probabilistic approach has been demonstrated
theoretically, it would benefit from application to more
complex experimental systems. The probabilistic approach
in vitro may also be helpful in developing the stochastic or
probability density-based biological theories needed to
treat in vivo enzyme kinetics in the cell. Our effort to
correlate in vitro and in vivo kinetics should strengthen the
ability of biochemical kinetics to elucidate biomolecular
functions, metabolism and the expression and transmission
of genetic information.
Acknowledgements
We would like to thank Prof. Dr. Ecaterina Putz from
the Economics Faculty of the West University of
Timioara for enlightening discussions about logistic
functions and methods. The authors are also very grateful
to Prof. Dr. Kathleen Swallow from Massachusetts
Institute of Technology and Merrimack College for
constructive discussions and careful reading of the
manuscript during her visit to the Chemistry Department
of West University of Timioara, in year 2006. The
financial support from Romanian National Council of
Scientific Research in Universities CNCSIS (by Grant
AT/54/2006-2007) is kindly appreciated as well.
References

4. Conclusions
This work provides both a new interpretation and a
new equation for Michaelis-Menten enzyme kinetics in
vitro. We interpret the reaction between a substrate and an
enzyme as a probabilistic process of physical-chemical
binding. A set of constraints on the reactive and unreactive
probabilities is also given. In this context the MichaelisMenten unreactive term has the same form as the first
order approximation of the more general logistic
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binding. The logistic version of the Michaelis-Menten
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and analyzing enzymic kinetics. It has also been proved
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substrate binding ranges and thus characterizes only fast
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M. V. Putz, A. M. Lacrm, V. Ostafe

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________________________

Corresponding author: mvputz@cbg.uvt.ro;

mv_putz@yahoo.com